Connexin 43 channels are essential for normal bone structure and osteocyte viability

Journal of Bone and Mineral Research

Volumn 30, Issue 3, 2015, Pages 550-562

  Xu, Huiyun ^a,b   Gu, Sumin ^b   Riquelme, Manuel A ^b   Burra, Sirisha ^b   Callaway, Danielle ^b   Cheng, Hongyun ^b   Guda, Teja ^d   Schmitz, James ^c   Fajardo, Roberto J ^c   Werner, Sherry L ^b   Zhao, Hong ^e   Shang, Peng ^a   Johnson, Mark L ^e   Bonewald, Lynda F ^e   Jiang, Jean X ^b  

^a NORTHWESTERN POLYTECHNICAL UNIVERSITY   (China)

^b Mays Cancer Center at UT Health San Antonio   (United States)

^c UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^d The University of Texas at San Antonio   (United States)

^e UNIVERSITY OF MISSOURI KANSAS CITY SCHOOL OF DENTISTRY   (United States)

Author keywords

Analysis quantitation of bone; Animal models; CX43; Osteocytes

Indexed keywords

CONNEXIN 43; GJA1 PROTEIN, MOUSE;

ANIMAL CELL; APOPTOSIS; ARTICLE; BONE DENSITY; BONE MARROW; BONE REMODELING; BONE STRUCTURE; CELL DEATH; CELL VIABILITY; COMPUTER ASSISTED TOMOGRAPHY; CONTROLLED STUDY; CORTICAL BONE; GAP JUNCTION; MOUSE; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLAST; OSTEOCYTE; OSTEOLYSIS; PERIOSTEUM; PHENOTYPE; PROTEIN EXPRESSION; TISSUE SECTION; TRABECULAR BONE; TRANSGENIC MOUSE; ANATOMY AND HISTOLOGY; ANIMAL; BONE; CELL SURVIVAL; CYTOLOGY; GENETICS; PHYSIOLOGY;

ANIMALS; BONE AND BONES; BONE DENSITY; CELL SURVIVAL; CONNEXIN 43; MICE; MICE, TRANSGENIC; OSTEOCYTES;

EID: 84922879487     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.2374     Document Type: Article

References (44)

1. Rochefort GY, Pallu S, Benhamou CL. Osteocyte: The unrecognized side of bone tissue. Osteoporos Int. 2010 Sep;21(9): 1457-69.
2. Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011;26: 229-38.
3. Bonewald LF. Generation and function of osteocyte dendritic processes. J Musculoskelet Neuronal Interact. 2005;5: 321-4.
4. Kato Y, Windle JJ, Koop BA, Mundy GR, Bonewald LF. Establishment of an osteocyte-like cell line. MLO-Y4. J Bone Miner. Res. 1997;12: 2014-23.
5. Cheng B, Zhao S, Luo J, Sprague E, Bonewald LF, Jiang JX. Expression of functional gap junctions and regulation by fluid flow shear stress in osteocyte-like MLO-Y4 cells. J Bone Miner Res. 2001;16: 249-59.
6. Cherian PP, Siller-Jackson AJ, Gu S, et al. Mechanical strain opens connexin 43 hemichannels in osteocytes: A novel mechanism for the release of prostaglandin. Mol Biol Cell. 2005;16: 3100-6.
7. Loiselle AE, Jiang JX, Donahue HJ. Gap junction and hemichannel functions in osteocytes. Bone. 2013;54: 205-12.
8. Goodenough DA, Goliger JA, Paul DL. Connexins, connexons, and intercellular communication. Annu Rev Biochem. 1996;65: 475-502.
9. Chung DJ, Castro CH, Watkins M, et al. Low peak bone mass and attenuated response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43. J Cell Sci. 2006;119: 4187-98.
10. Grimston SK, Brodt MD, Silva MJ, Civitelli R. Attenuated response to in vivo mechanical loading in mice with conditional osteoblast ablation of the connexin43 gene (Gja1). J Bone Miner Res. 2008;23: 879-86.
11. Zhang Y, Paul EM, Sathyendra V, et al. Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone. PLoS One. 2011;6: E23516.
12. Reaume AG, De Sousa PA, Kulkarni S, et al. Cardiac malformation in neonatal mice lacking connexin43. Science. 1995;267: 1831-4.
13. Lecanda F, Warlow PM, Sheikh S, Furlan F, Steinberg TH, Civitelli R. Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction. J Cell Biol. 2000;151: 931-43.
14. Grimston SK, Screen J, Haskell H, et al. Role of connexin43 in osteoblast response to physical load. Ann N Y Acad Sci. 2006;1068: 214-24.
15. Plotkin LI, Lezcano V, Thostenson J, Weinstein RS, Manolagas SC, Bellido T. Connexin 43 is required for the anti-apoptotic effect of bisphsphonates on osteocytes and osteoblasts in vivo. J Bone Miner Res. 2008;23: 1712-21.
16. Watkins M, Grimston SK, Norris JY, et al. Osteoblast connexin43 modulates skeletal architecture by regulating both arms of bone remodeling. Mol Biol Cell. 2011;22: 1240-51.
17. Flenniken AM, Osborne LR, Anderson N, et al. A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia. Development. 2005;132: 4375-86.
18. Zappitelli T, Chen F, Moreno L, et al. The G60S connexin 43 mutation activates the osteoblast lineage and results in a resorptionstimulating bone matrix and abrogation of old-age-related bone loss. J Bone Miner Res. 2013;28: 2400-13.
19. Bivi N, Condon KW, Allen MR, et al. Cell autonomous requirement of connexin 43 for osteocyte survival: Consequences for endocortical resorption and periosteal bone formation. J Bone Miner Res. 2011;27: 374-89.
20. Ajubi NE, Klein-Nulend J, Nijweide PJ, Vrijheid-Lammers T, Alblas MJ, Burger EH. Pulsating fluid flow increases prostaglandin production by cultured chicken osteocytes-A cytoskeleton-dependent process. Biochem Biophys Res Commun. 1996;225: 62-8.
21. Genetos DC, Kephart CJ, Zhang Y, Yellowley CE, Donahue HJ. Oscillating fluid flow activation of gap junction hemichannels induces ATP release from MLO-Y4 osteocytes. J Cell Physiol. 2007;212: 207-14.
22. Baylink TM, Mohan S, Fitzsimmons RJ, Baylink DJ. Evaluation of signal transduction mechanisms for the mitogenic effects of prostaglandin E2 in normal human bone cells in vitro. J Bone Miner Res. 1996;11: 1413-8.
23. Keller J, Klamer A, Bak B, Suder P. Effects of local prostaglandin E2 on fracture callus in rabbit. Acta Orthop Scand. 1993;64: 59-63.
24. JeeWSS, Ueno K, Deng YP, WoodburyDM. The effects of prostaglandin E2 in growing rats: Increased metaphyseal hard tissue and corticoendosteal bone formation. Calcif Tissue Int. 1985;37: 148-56.
25. Yang W, Kalajzic I, Lu Y, et al. Identification of an osteocyte-specific mechanically regulated region of the dentin matrix protein 1 gene. J Biol Chem. 2005;280: 20680-90.
26. Gu SM, Thompson DA, Srikumari CR, et al. Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nat Genet. 1997;17: 194-7.
27. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29: E45.
28. Stern AR, Stern MM, Van Dyke ME, Jähn K, Prideaux M, Bonewald LF. Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice. Biotechniques. 2012;52: 361-73.
29. Fajardo RJ, Muller R, Ketcham RA, Colbert M. Nonhuman anthropoid primate femoral neck trabecular architecture and its relationship to locomotor mode. Anat Rec. 2007;290: 422-36.
30. Fajardo RJ, Desilva JM, Manorharan RK, Schmitz JE, MacLatchy LM, Bouxsein ML. Lumbar vertebral body bone microstructural scaling in small to medium-sized strepsirhines. Anat Rec (Hoboken). 2013; 296: 210-26.
31. Deng Y, Chen Y, Reuss L, Altenberg GA. Mutations of connexin 26 at position 75 and dominant deafness: Essential role of arginine for the generation of functional gap-junctional channels. Hear Res. 2006; 220: 87-94.
32. Wang M, Martinez AD, Berthoud VM, et al. Connexin43 with a cytoplasmic deletion inhibits the function of several connexins. Biochem Biophys Res Commun. 2005;333: 1185-93.
33. Plotkin LI, Manolagas SC, Bellido T. Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem. 2002;277: 8648-57.
34. Siller-Jackson AJ, Burra S, Gu S, et al. Adaptation of connexin 43-hemichannel prostaglandin release to mechanical loading. J Biol Chem. 2008;283: 26374-82.
35. Kitase Y, Barragan L, Qiang H, et al. Mechanical induction of PGE2 in osteocytes blocks glucocorticoid-induced apoptosis through both the b-catenin and PKA pathways. J Bone Miner Res. 2010;25: 2381-92.
36. Kalajzic I, Matthews BG, Torreggiani E, Harris MA, Pajevic PD, Harris SE. In vivo and in vitro approaches to study osteocyte biology. Bone. 2013 Jun;54(2): 296-306.
37. Gluhak-Heinrich J, Gu S, Pavlin D, Jiang JX. Mechanical loading stimulates expression of connexin 43 in alveolar bone cells in the tooth movement model. Cell Commun Adhes. 2006;13: 115-25.
38. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473: 139-46.
39. Liu XH, Kirschenbaum A, Yao S, Levine AC. Interactive effect of interleukin-6 and prostaglandin E2 on osteoclastogenesis via the OPG/RANKL/RANK system. Ann N Y Acad Sci. 2006;1068: 225-33.
40. Ramirez-Yanez GO, Symons AL. Prostaglandin E2 affects osteoblast biology in a dose-dependent manner: An in vitro study. Arch Oral Biol. 2012;57: 1274-81.
41. Jurado S, Garcia-Giralt N, Diez-Perez A, et al. Effect of IL-1beta, PGE(2), and TGF-beta1 on the expression of OPG and RANKL in normal and osteoporotic primary human osteoblasts. J Cell Biochem. 2010;110: 304-10.
42. Nakashima T, Hayashi M, Fukunaga T, et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17: 1231-4.
43. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011;17: 1235-41.
44. Taylor AF, Saunders MM, Shingle DL, Cimbala JM, Zhou Z, Donahue HJ. Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions. Am J Physiol Cell Physiol. 2007;292: C545-52.